tert-Butyl piperazine-1-carboxylate → HCID 67380950, compound

HRID 1804004Notes

Reaction equation

HRID 1804004 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[N:6][C:5]([CH3:9])=[CH:4][N:3]=1.[C:10]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:13]([O:12][C:10]([N:17]1[CH2:22][CH2:21][N:20]([C:2]2[C:7]([CH3:8])=[N:6][C:5]([CH3:9])=[CH:4][N:3]=2)[CH2:19][CH2:18]1)=[O:11])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 116726802-Chloro-3,5-dimethylpyrazineHCID 23676156Sodium t-butoxide

Product 1

HCID 67380950HCID 67380950, compoundYield 87.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

To a mixture of 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium (II) acetate (225 mg), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (953 mg) and sodium tert-butoxide (2.7 g) was added toluene (40 mL), and the mixture was refluxed for 8 hr. After cooling, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 3′,5′-dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g). 3′,5′-Dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL) was added, and the mixture was stirred at room temperature overnight. Ethyl acetate (100 mL) was added, and the mixture was filtered to give the title compound (3.3 g).

Workup

  1. temperaturethe mixture was refluxed for 8 hr
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated
  6. customThe residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-20ac5da42d1b4852bee59438de77f2b2
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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